Alkene stereochemistry

Furthei-more, the cyclization of the iododiene 225 affords the si.x-membered product 228. In this case too, complete inversion of the alkene stereochemistry is observed. The (Z)-allylic alcohol 229 is not the product. Therefore, the cyclization cannot be explained by a simple endo mode cyclization to form 229. This cyclization is explained by a sequence of (i) e.vo-mode carbopallada-tion to form the intermediate 226, (ii) cydopropanation to form 227. and (iii) cyclopropylcarbinyl to homoallyl rearrangement to afford the (F3-allylic alcohol 228[166]. (For further examples of cydopropanation and endo versus e o cyclization. see Section 1.1.2.2.)... 

Finally, in a study of Lewis-acid-catalysed intramolecular attack of acetals on vinylsilanes, to produce allylically unsaturated oxacyclics, it has been found (75) that the alkene stereochemistry can control the mode of cyclization in an exo- or endocyclic sense, as shown here ... 

Further variations on the epoxyketone intermediate theme have been reported. In the first (Scheme 9A) [78], limonene oxide was prepared by Sharpless asymmetric epoxidation of commercial (S)-(-)- perillyl alcohol 65 followed by conversion of the alcohol 66 to the crystalline mesylate, recrystallization to remove stereoisomeric impurities, and reduction with LiAlH4 to give (-)-limonene oxide 59. This was converted to the key epoxyketone 60 by phase transfer catalyzed permanganate oxidation. Control of the trisubstituted alkene stereochemistry was achieved by reaction of the ketone with the anion from (4-methyl-3-pentenyl)diphenylphosphine oxide, yielding the isolable erythro adduct 67, and the trisubstituted E-alkene 52a from spontaneous elimination by the threo adduct. Treatment of the erythro adduct with NaH in DMF resulted... 

AIBN, (67) forms in high yield because the initial radical abstracts the hydrogen a to the carbonyl (with concomitant elimination of BusSn) more rapidly than it cyclizes. However, blocking this pathway results in smooth ring expansion, as illustrated by the conversion of (66) to (68). The alkene stereochemistry is dictated by the configuration of the precursor (see Scheme 49). 

The 1,1-cycloaddition process also occurs in nonphotolytic reactions involving azomethine ylides. Thermolysis of oxazolinone (147) led to a 3,5-fused bicyclic dihydropyrrole in 80% yield.72 The alkene stereochemistry was maintained in the product, although subsequent photolysis scrambled the methyl and trideuteromethyl groups. Nondeuterated oxazolinone gave the cyclization product which was converted to a dihydropyridine on warming with acid.74... 

Azomethine imines which contain an intervening aromatic ring between the dipole and dipolarophile are accessible from aryl aldehydes and readily undergo cyclization. Thus, imine (154), where the dipolarophile is attached at the carbon of the dipole, afforded cis- and rrans-fused tricyclic pyrazolidines in which the alkene stereochemistry was retained (Scheme 48).78 ... 

In contrast to the above results, the diazo compounds (182a-b) with a one-carbon intervening chain underwent exclusive 1,1-cycloaddition.97 These cyclizations were stereospecific the alkene stereochemistry was retained.97-99... 

By considering the H-migration origin/destination, one may distinguish I, II and III/IV. On this basis, experiments (i) and (ii) with a type A catalyst as shown in Scheme 12.9 eliminated mechanisms I and II from consideration this left III and IV which were both fully consistent with the results. The outcome for (i) is obvious the allylic hydrogens (see Hb in mechanism I, Scheme 12.8) are not involved in the reaction. The outcome for (ii) is more subtle and relates to the stereochemistry attending fceta-carbopalladation and beta-hydride elimination which are both known to proceed with syn stereochemistry. Thus, mechanism II which does not involve a beta-hydride elimination would not affect the alkene stereochemistry (see Hc in II, Scheme 12.8), as was revealed by D-labelling, Scheme 12.9. In contrast, mechanisms III and IV should reverse the stereochemistry (see Hc in III and IV, Scheme 12.8), as was observed. 

The use of perfluoroalkyliodide in group transfer tandem additions has been examined by Wang and Lu for the preparation of butyrolactones [95T2639]. The mild reaction conditions, high chemical yield, and excellent control of alkene stereochemistry are the highlights of this methodology. 

In aryl and vinyl bromides and iodides, silylation has been performed by reaction with tris(trimethylsilyl)aluminum etherate in the presence of a nickel(II) chloride-triphenylphosphine complex381. In vinyl iodides the alkene stereochemistry is retained but it is lost in bromides. 

Perfluoroalkylation of vinyl halides has seen some recent attention. The use of trifluoro-methyl- and pentafluoroethylcopper has been mentioned previously12,13. Furthermore, vinyl iodides and bromides have been trifluoromethylated and pentafluoroethylated by the reaction of these substrates with the appropriate trialkylsilanes in the presence of stoichiometric amounts of potassium fluoride and Cul23. Only 1,2-disubstituted vinyl halides have been used as substrates, and iodides are apparently somewhat more suitable substrates. Preservation of alkene stereochemistry appears to be good in these transformations (equation 18). 

The coupling of vinyl halides and alkynes has been found to be induced by either stoichiometric amounts of Cul29, or catalytic amounts of Cul in the presence of PPh3 and K2C0330. Disubstituted iodides and bromides are both suitable substrates, and alkene stereochemistry is once again preserved (equation 21). 

Procter has suggested that a study of the dependence of reaction outcome on the stereochemistry of the alkene in the substrate can be used to gain information on the mechanistic direction of reductive couplings.42,43 In cases where the alkene stereochemistry has a marked effect on the reaction outcome, a traditional carbonyl first mechanism may be in operation, whereas in reactions where alkene stereochemistry has little effect, an alternative mechanism in which the alkene is reduced first and a common reactive intermediate is formed, regardless of the geometry of the starting alkene, may operate (Scheme 5.20).42,43... 

Alkene stereochemistry in the Claisen rearrangement comes from a chair-like transition state... 

Although an energetically less favourable sp2 to sp3 carbanion transformation is involved in these processes, both aryllithium and vinyllithium cyclizations onto alkenes are successful. Moreover, cyclization reactions of vinyllithiums, rather than alkyllithiums, would also incorporate additional functionality (an alkene) into the product, allowing the preparation of alkylidenecycloalkanes with control of the alkene stereochemistry. 

The main feature of tin to hthium exchange is the preservation of the alkene stereochemistry, which was already demonstrated in 1964 . In conjunction with the easy access to stereodefined alkenyltins, this feature has been extensively exploited for synthetic purposes such as the construction of prostaglandins side chains and unsaturated fatty acids ° ° , the syntheses of a macrocyclic lactone , brefeldin cerulenin... 

Alkenyllithium compounds can also be prepared by metaUation of alkenes, particularly when alkenyl hydrogens are rendered acidic by an a-substituent (equation 22). Transmetallation of alkenyl stannanes with organohthium reagents gives alkenyUithium compounds with retention of alkene stereochemistry (equation 23). Tin lithium fransmet-allation has been used to prepare 1,4-dihthio-l,3-butadiene. Monosubstituted alkenylhthium compounds RHC=CHLi, can also be prepared from the corresponding diorganotel-luride, RHC=CHTeBu, by reaction with butylhthium in... 

When electron deficient alkenes are added to cyclopropene derivatives (74 equation 33) and (77 equation 34) in the presence of [Ni(COD)2], vinylcyclopropanes are formed in good yields. For example, dialkyl fumarate or maleate reacts with 3,3-dimethylcyclopropene in the presence of [Ni(COD)2] to give 2,3-bis(alkoxycarbonyl)-l-(2-methyl-l-propenyl)cyclopropanes (75), (76), (78) and (79), in which alkene stereochemistry is chiefly retained, in 50-73% yields. Reaction of methyl acrylate with 3,3-dimethylcyclopropene results in the formation of several products, while reaction of methyl acrylate with 3,3-diphenylcyclopropene gives vinylcyclopropane derivatives (80 equation 35) in 85% yield. Under similar conditions, methyl crotonate reacts with (74a) to give (82) in low yield (equation 36). Catalysis with nickel(0)/PR3, 2 [Ni(CO)4], 3 [Pd(DBA)2] or [Pd(DBA)2]/PlV33 gives mainly... 

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